UBE2C is overexpressed in ESCC tissues and its abrogation attenuates the malignant phenotype of ESCC cell lines.

Antonio Palumbo,Pedro Nicolau Neto,Nathalia Meireles Da Costa,Vanessa Paiva Leite De Sousa,Luis Felipe Ribeiro Pinto,Anke Bergman,Simona Pellecchia,Luiz Eurico Nasciutti,Cleber Dario Kruel,Alfredo Fusco,Romina Sepe,Marco De Martino

doi:10.18632/oncotarget.11674

Abstract

The esophageal squamous cell carcinoma (ESCC) is widely known as a highly lethal and poor understood cancer, then requiring the search for novel molecular markers to improve its management and patients survival. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been figuring as a prominent tumor biomarker candidate, once it has been recognized as a key player in cell cycle progression. In this way, the aim of this study was to evaluate the expression profile of UBE2C gene and protein in ESCC samples, as well as its diagnostic and prognostic marker potential, and its contribution to ESSC genesis and/or progression by performing in vitro functional assays. The analysis of UBE2C gene expression in 52 paired ESCC samples (tumor and respective histologically normal surrounding tissue), by qRT-PCR, revealed that this gene is overexpressed in 73% of ESCC samples. Subsequently, immunohistochemical analysis confirmed that UBE2C protein expression was upregulated in all ESCC cases, but absent in the histologically normal tumor surrounding tissues. Moreover, we showed that UBE2C mRNA expression was able to accurately discriminate ESCC tissue from both healthy esophageal and histologically normal tumor surrounding tissues, pointing out its role as a diagnostic marker for this cancer. Finally, we report that UBE2C affects proliferation rates and cell cycle profile of ESCC cell lines, by directly interfering with cyclin B1 protein levels, suggesting its involvement in crucial steps of ESCC carcinogenesis.

Highlights

The esophageal cancer (EC) figures as a highly lethal tumor that responds for the eighth position in cancer incidence worldwide [1]
Our results show that ubiquitinconjugating enzyme E2C (UBE2C) is highly expressed in esophageal squamous cell carcinoma (ESCC) samples, but not in normal mucosa, and that its abrogation is capable of altering proliferation and cell cycle profile of ESCC cell lines, by directly interfering with cyclin B1 protein levels
It has been reported that the expression, and the crucial role played by ubiquitin conjugating enzyme UBE2C in the cell cycle progression are altered in several types of cancer [10,11,12,13,14]

Summary

Introduction

The esophageal cancer (EC) figures as a highly lethal tumor that responds for the eighth position in cancer incidence worldwide [1]. A known correlation between the high lethality displayed by ESCC and its late stage detection has been related as one of the main causes that contribute to the unsuccessful treatment in this disease management [3]. Despite the evolution in cancer detection and treatment [4, 5], the molecular alterations involved in the ESCC carcinogenesis remain poorly understood [3]. The identification of new biomarkers and www.impactjournals.com/oncotarget the definition of their roles in the ESCC development could greatly contribute to the improvement of disease diagnosis and therapy. It has been already shown that high UBE2C expression is related with a highly malignant phenotype and a poor survival suggesting its role in cancer progression [12, 15, 16, 17, 18]

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Conclusion